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Abnormal procainamide pharmacokinetics (prolonged half-life and decreased volume of distribution) and pharmacodynamics (decreased threshold for the suppression of premature ventricular complexes) have been suggested in patients with acute myocardial infarction or congestive heart failure, or both. To better define procainamide kinetics, 37 patients in the acute care setting received intravenous procainamide (25 mg/min, median dose 750 mg) with peak and hourly blood samples taken over 6 hours. Compared with the 10 control patients, the 12 patients with acute myocardial infarction and the 15 patients with congestive heart failure had normal procainamide pharmacokinetics with respect to half-life (2.3 +/- 1.0, 2.5 +/- 0.9 and 2.6 +/- 0.8 hours, respectively), volume of distribution (1.9 +/- 0.7, 1.8 +/- 0.4 and 1.8 +/- 0.5 liters/kg, respectively), clearance (11.3 +/- 7.5, 9.3 +/- 3.6 and 9.1 +/- 3.5 ml/min per kg, respectively) and unbound drug fraction (66 +/- 9, 66 +/- 9 and 69 +/- 4%, respectively). Low thresholds for greater than 85% premature ventricular complex suppression were confirmed in these patients (median 4.7 micrograms/ml in patients with acute myocardial infarction and 3.3 micrograms/ml in patients with congestive heart failure). Thus, differences in the response of premature ventricular complexes to procainamide reflect electropharmacologic differences dependent on clinical setting rather than pharmacokinetic abnormalities. Furthermore, the reduction of procainamide dosing in patients with acute myocardial infarction or congestive heart failure, based solely on prior kinetic data, may result in inappropriate antiarrhythmic therapy.

We describe a single-run method for quantitating quinidine, procainamide, and N-acetylprocainamide, involving gas-liquid chromatography with a nitrogen-phosphorus selective detector. Within-run precision (CV) was 3% (x = 2 mg/L, n = 20), 6.9% (x = 4 mg/L, n = 10), and 1.5% (x = 8 mg/L, n = 8) for quinidine; 7.7% (x = 4 mg/L, n = 14), 1.6% (x = 8 mg/L, n = 16), and 2.3% (x = 12 mg/L, n = 12) for procainamide; and 6.3% (x = 5 mg/L, n = 6), 3.6% (x = 10 mg/L, n = 20), and 4.0% (x = 20 mg/L, n = 10) for N-acetylprocainamide.l Between-run precision was 3.0%(x = 2 mg/L, n = 20), 7.0% (x = 4 mg/L, n = 9), and 2.8% (x = 8 mg/L, n = 9) for quinidine; 4.7% (x = 4 mg/L, n = 10). 3.3% (x = 8 mg/L, n = 20), and 1.9% (x = 12 mg/L, n = 10) for procainamide; and 9.3% (x = 5 mg/L, n = 6), 4.3% (x = 10 mg/L, n = 20), and 3.8% (x = 20 mg/L, n = 10) for N-acetylprocainamide. Tube stoppers that contain a rubber plasticizer interfere with the technique. Clinical application and correlation with drug concentrations by this technique are discussed.

We have previously reported an increased prevalence of elevated blood pressure in Hispanic adolescent males. The pressure elevation did not correlate with weight. In this study, we evaluated the response to antihypertensive therapy of eight adolescent Hispanic males found to have elevated pressure during high school screening. All patients were placed on placebo tablets b.i.d. for 2 weeks with weekly blood pressure readings. Those with persistently elevated pressures (at or above the 95th percentile) underwent laboratory testing, exercise testing, and echocardiography. An age-matched group of Hispanic adolescents with blood pressure recording below the 90th percentile were also exercised. Patients were then placed on 0.1 mg clonidine b.i.d. for 12 weeks. Pretherapy exercise testing demonstrated an abnormal systolic hypertensive response (mean 193 +/- 43 mmHg) that improved after therapy (mean 167 +/- 28 mmHg). Echocardiographic data were normal. All patients had elevated levels of VLDL and triglycerides. Five patients also had HDL levels below the 50th percentile for age and sex. We conclude that this population is similar to other hypertensive adolescent populations in exercise response pre- and posttherapy with clonidine, but they demonstrated a unique clinical feature in the elevation of the VLDL and triglyceride lipoprotein fractions.

Pharmacodynamic and pharmacokinetic aspects pertinent to the potential clinical application of unbound quinidine levels were studied. Following heparin administration during electrophysiologic testing in 10 patients receiving quinidine, there were significant increases in the mean (+/- SD) right ventricular effective refractory period (266 +/- 24 versus 279 +/- 23; p less than 0.025), free fatty acid concentration (515 +/- 213 versus 1071 +/- 359 mmol/L; p less than 0.001), and unbound quinidine concentration (0.3 +/- 0.1 to 0.6 +/- 0.1 microgram/ml; p less than 0.001) but no changes in heart rate, corrected QT interval, or total plasma quinidine concentration. Ten control patients showed no change in the right ventricular effective refractory period following heparin administration. These findings were consistent with a heparin-induced increase in unbound drug concentration and activity that was limited to the vascular compartment. Eleven patients studied on day 3 (+/- 1) and day 10 (+/- 3) during an acute myocardial infarction showed a significant decrease in unbound quinidine fraction (12 +/- 4% versus 9 +/- 4%; p less than 0.02) accompanied by a decrease, rather than the predicted increase, in half-life (7.1 +/- 2.7 versus 6.3 +/- 2.1 hours; p less than 0.02). Volumes of distribution remained stable while the mean quinidine clearance tended to increase. Half-life correlated with albumin changes (r = -0.71; p less than 0.02). Apparently, improvement in clinical status (assumed) and drug clearance (measured) negated the direct effects of the decrease in unbound quinidine fraction. Although unbound drug concentrations should correlate best with drug dynamic and kinetic information, full knowledge of the clinical context of such measurements is needed for appropriate interpretation.

This study was undertaken to better characterize the role of multiform premature ventricular complexes in the classification of ventricular arrhythmias based on form and frequency. Twenty inpatients with organic heart disease and multiform ventricular complexes underwent continuous electrocardiographic monitoring with full disclosure analysis of the number and morphology of single premature ventricular complexes, of repetitive forms of greater than or equal to 2 premature ventricular complexes, and of the variability of coupling intervals (greater than or equal to 40 msec). Multiform premature ventricular complexes were of 3 +/- 1.4 (mean +/- S.D.) different QRS morphologies. Nineteen patients (95%) had repetitive forms of greater than or equal to 2 premature ventricular complexes; 18 patients (90%) showed variable coupling (125 +/- 29 msec). Repetitive forms or variable coupling were present in each (100%) of the 20 patients studied. These data suggest that multiform premature ventricular complexes may be a transitional arrhythmia, since repetitive forms almost always coexist. Variability in coupling, rather than just form and frequency, may be an electrocardiographic characteristic linking single and repetitive forms.

Clinical, angiographic, and pathologic data support the contention that atherosclerosis, platelet aggregation, and coronary vasomotility work in unison to cause coronary thrombosis, which in turn leads to myocardial infarction. A patient is described in whom, 2 months after an acute myocardial infarction, inducible coronary artery spasm and a nonocclusive thrombus were angiographically demonstrated at the site of a minimal atherosclerotic narrowing in the infarction-related vessel. This report, to the best of our knowledge, is the first time that these three pathophysiologic mechanisms have been shown, in vivo, to be occurring concomitantly in an infarct-related vessel. Documentation of the unified occurrence of these phenomena support the current concept of the pathophysiology of myocardial infarction.

The effect of an infusion of intravenous procainamide on the frequency of ventricular premature complexes (VCPs) of differing QRS morphologies was studied in 20 patients with multiform ectopic activity. In 17 of 20 patients, there was differential suppression of single VPCs with different QRS morphologies. VPCs of the most frequent QRS morphology and the second most frequent QRS morphology were compared with respect to the procainamide level at the escape of VPCs from 85% suppression and the duration of suppression measured from the onset of the procainamide infusion. In 8 patients, VPCs of the most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the second most frequent QRS morphology (escape procainamide concentration = 2.8 +/- 1.7 versus 5.4 +/- 2.3 micrograms/ml, p less than 0.025; time to escape 244 +/- 138 versus 98 +/- 114 min; p less than 0.05). In 9 other patients, VPCs of the second most frequent QRS morphology remained suppressed at lower procainamide concentrations and for longer times than did VPCs of the most frequent QRS morphology (escape procainamide concentration 2.9 +/- 1.4 versus 8.3 +/- 6.3 micrograms/ml, p less than 0.025; time to escape 317 +/- 114 versus 63 +/- 80 min; p less than 0.001). Thus, in individual patients there are specific patterns of suppression of VPCs of different QRS morphologies which are independent of the frequency of each morphology. There is apparently a differential pharmacologic effect of procainamide on the foci or pathways responsible for the different QRS morphologies of multiform VPCs.

Echocardiography and systolic time-interval measurements were performed to assess left ventricular size and function in 15 women receiving oral contraceptives and in a control group. There was no significant difference in heart rate (78 +/- 9 verus 72 +/- 12 beats/min), blood pressure (116 +/- 8/72 +/- 7 versus 110 +/- 11/67 +/- 9 mmHg), left ventricular ejection time/preejection period (LVET/PEP) (0.31 +/- 0.05 versus 0.29 +/- 0.05), left ventricular internal dimension in diastrol (4.3 +/- 0.3 versus 4.3 +/- 0.5 cm) or systole (2.7 +/- 0.3 versus 2.6 +/- 0.4 cm), shortening fraction (0.37 +/- 0.05 versus 0.41 +/- 0.05), or mean normalized velocity of circumferential shortening (1.30 +/- 0.21 versus 1.31 +/- 0.23). Therefore, young, healthy women receiving oral contraceptives do not appear to be at increased risk with respect to abnormalities of ventricular volume or contraction.

We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.

New balloon-on-a-wire dilation systems allow crossing of severely stenosed coronary arteries owing to their ultra-low profile. However, these systems do not allow for over-the-wire exchange to a larger balloon catheter or insertion of perfusion catheters, should the vessel close abruptly during dilation. Therefore, if the need for such catheters arises, the vessel must be left unprotected during attempts to recross the lesion. We describe a new technique using a combined balloon-on-a-wire system and an exchangeable guidewire, which permits the crossing and dilation of severely stenosed coronary arteries, while at the same time offering vessel protection and balloon catheter exchange.